Overcoming Oral Delivery Barriers for Therapeutic Proteins and Peptides: Current Strategies Review | Research

The takeaway

Current oral protein/peptide delivery strategies including nanoparticles, lipid systems, permeation enhancers, and enzyme inhibitors show progress but bioavailability remains limited, requiring multi-barrier approaches.

<10% barrier
Despite numerous strategies, oral peptide bioavailability typically remains below 10% — the persistent challenge of oral peptide drug delivery

What the researchers found

Current oral peptide delivery strategies (NPs, lipids, permeation enhancers, enzyme inhibitors, targeted release) show progress but bioavailability remains typically <10%, requiring integrated multi-barrier approaches.

Why it matters

Most peptide drugs require injection. Solving oral delivery would transform treatment adherence for millions of patients.

How the study worked

Review of functional food protein/peptide oral delivery technologies, covering barriers, strategies, and current bioavailability limitations.

What this study cannot tell us

Most studies in vitro or animal. Human oral bioavailability consistently lower than preclinical predictions.

How to read the evidence

Comprehensive review of delivery technologies and their current limitations.

When this study was published

Published in 2025.

The bigger picture

Oral peptide delivery is the holy grail of pharmaceutical formulation — solving it would affect insulin, GLP-1, AMPs, and countless other peptide drugs.

Questions still open

Will combination strategies achieve >20% oral bioavailability?
Can AI predict optimal formulation-peptide combinations?
When will oral insulin with meaningful bioavailability reach market?

Common questions

Why can't most peptide drugs be taken as pills?

Stomach acid destroys them, digestive enzymes break them down, and the intestinal wall blocks absorption. Current solutions improve this but typically deliver less than 10% of the dose.

What is the best oral peptide delivery approach?

No single approach works well alone. The most promising strategies combine protection (nanoparticles), absorption enhancement (permeation enhancers), and targeted intestinal release simultaneously.

Read the original research

Overcoming oral delivery barriers of functional proteins: current status and advanced delivery technologies.

Food chemistry, 503, 147818

View on PubMed ↗Publisher’s paper ↗

Citation

Jianghao, Zhang; Shadrack, Salumu Masuwa; Mingcheng, Wang; Shichao, Mi; Mengjia, Chu; Rakariyatham, Kanyasiri; McClements, David Julian; Chongjiang, Cao; Xiao, Xu; Biao, Yuan. (2026). Overcoming oral delivery barriers of functional proteins: current status and advanced delivery technologies.. Food chemistry, 503, 147818. https://doi.org/10.1016/j.foodchem.2025.147818